Author:

Keywords:

Marrow-Derived Cells, Endothelial-Cells, Lentiviral Vectors, Stem-Cells, In-Vivo, Angiogenesis, Precursors, Growth, Vegf, Vascularization, Science & Technology, Life Sciences & Biomedicine, Oncology, Cell Biology, MARROW-DERIVED CELLS, ENDOTHELIAL-CELLS, IN-VIVO, ANGIOGENESIS, STEM, PRECURSORS, VASCULARIZATION, TRANSPLANTATION, ANGIOPOIETIN-1, PROGRESSION, Animals, Genes, Reporter, Genetic Vectors, Glioblastoma, Green Fluorescent Proteins, Humans, Mesoderm, Mice, Mice, Nude, Mice, SCID, Mice, Transgenic, Monocytes, Neovascularization, Pathologic, Pancreatic Neoplasms, Pericytes, Receptor, TIE-2, Stem Cells, Transplantation, Heterologous, 1109 Neurosciences, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, 3101 Biochemistry and cell biology, 3211 Oncology and carcinogenesis

Abstract:

Bone marrow-derived cells contribute to tumor angiogenesis. Here, we demonstrate that monocytes expressing the Tie2 receptor (Tie2-expressing monocytes [TEMs]) (1) are a distinct hematopoietic lineage of proangiogenic cells, (2) are selectively recruited to spontaneous and orthotopic tumors, (3) promote angiogenesis in a paracrine manner, and (4) account for most of the proangiogenic activity of myeloid cells in tumors. Remarkably, TEM knockout completely prevented human glioma neovascularization in the mouse brain and induced substantial tumor regression. Besides TEMs and endothelial cells (ECs), Tie2 expression distinguished a rare population of tumor stroma-derived mesenchymal progenitors representing a primary source of tumor pericytes. Therefore, Tie2 expression characterizes three distinct cell types required for tumor neovascularization: ECs, proangiogenic cells of hematopoietic origin, and pericyte precursors of mesenchymal origin.